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Trial record 1 of 1 for:    lm11a-31
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Study of LM11A-31-BHS in Mild-moderate AD Patients

This study is currently recruiting participants.
Verified February 2017 by PharmatrophiX Inc.
Sponsor:
ClinicalTrials.gov Identifier:
NCT03069014
First Posted: March 3, 2017
Last Update Posted: March 3, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
PharmatrophiX Inc.
  Purpose
The purpose of this study is to determine the safety of 2 doses of LM11A-31-BHS in 120 patients with Alzheimer's Disease versus placebo and to access biomarker and clinical exploratory endpoints of LM11A-31-BHS

Condition Intervention Phase
Mild to Moderate Alzheimer's Disease Drug: 400mg LM11A-31-BHS Drug: 800mg LM11A-31-BHS Drug: Placebos Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A 6-months Prospective, Multi-center, Double-blind, Placebo-controlled, Randomized, Adaptive-trial-design Study to Evaluate Safety, Tolerability and Exploratory Endpoints of Either Placebo or Two Different Oral Doses of LM11A-31-BHS in Patients With Mild to Moderate Probable Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by PharmatrophiX Inc.:

Primary Outcome Measures:
  • Number of AEs/SAEs within the 26-week study period [ Time Frame: 26 weeks ]
    number of subjects with AEs/SAEs, changes in vital signs and laboratory examinations


Secondary Outcome Measures:
  • Statistically relevant changes in CSF-Biomarkers between baseline and final visit [ Time Frame: 26 weeks ]
    CSF-Biomarkers (tau, ptau, Aβ40, Aβ42, AchE activity)

  • Statistically relevant changes in working memory ability between baseline and final visit assessed with the Controlled Oral Word Association Test (COWAT) [ Time Frame: 26 weeks ]
    Controlled Oral Word Association Test (COWAT)

  • Statistically relevant changes in word fluency between baseline and final visit assessed with the Category Fluency Test (CFT) [ Time Frame: 26 weeks ]
    Category Fluency Test (CFT)

  • Statistically relevant changes in processing speed between baseline and final visit assessed with the Coding Test (Subtest of the Wechsler Adult Intelligence Scale) [ Time Frame: 26 weeks ]
    Coding Test (Subtest of the Wechsler Adult Intelligence Scale)

  • Statistically relevant changes in executive functions between baseline and final visit assessed with the Digit Span test (Subtest of the Wechsler Adult Intelligence Scale) [ Time Frame: 26 weeks ]
    Digit Span test (Subtest of the Wechsler Adult Intelligence Scale)


Estimated Enrollment: 120
Actual Study Start Date: February 15, 2017
Estimated Study Completion Date: October 31, 2019
Estimated Primary Completion Date: October 10, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 400mg LM11A-31-BHS
400mg LM11A-31-BHS and 400mg Placebo per day
Drug: 400mg LM11A-31-BHS
2 Oral Capsules (200mg of LM11A-31-BHS and 200mg of placebo) twice daily (morning & evening) for 26 weeks
Drug: Placebos
2 Oral Capsules (200mg of Placebo) twice daily (morning & evening) for 26 weeks
Active Comparator: 800mg LM11A-31-BHS
800mg LM11A-31-BHS
Drug: 800mg LM11A-31-BHS
2 Oral Capsules (200mg of LM11A-31-BHS) twice daily (morning & evening) for 26 weeks
Placebo Comparator: Placebos
800mg (microcrystalline cellulose with 0.5 - 1% magnesium stearate) per day
Drug: Placebos
2 Oral Capsules (200mg of Placebo) twice daily (morning & evening) for 26 weeks

Detailed Description:

The goal of this AD Pilot is to conduct a prospective, double-blind, multicenter, phase IIa exploratory safety, feasibility and proof-of-concept trial in mild to moderate Alzheimer's disease patients with the orally bioavailable p75 neurotrophin receptor ligand LM11A-31-BHS dosed twice daily for 26 weeks. Successful completion of this trial will provide the safety, endpoint and statistical basis for the design and execution of a phase 2b/3 efficacy trial. It will also bring to the AD field a much-needed new set of target mechanisms and will help pioneer the strategy of the concomitant targeting of multiple fundamental AD-related pathological processes.

During the 26 weeks study period the eligible patients will be invited to 5 visits.

Safety monitoring will include the full extent of phase 2 clinical, electrophysiological and laboratory testing.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   50 Years to 85 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Men and women (non-childbearing potential) with a diagnosis of Alzheimer's disease according to McKhann (2011) criteria
  2. Age 50 - 85 years
  3. MRI or CT assessment within six months before baseline, corroborating the clinical diagnosis of AD and excluding other potential causes of dementia, especially cerebrovascular lesions (see exclusion criteria, number 3)
  4. CSF AD specific biomarker profile; positive, defined as CSF Aβ42 <530 ng l−1 together with either of T-tau>350 ng l−1 or p-tau >60 ng l−1
  5. Mild to moderate stage of Alzheimer's disease according to MMSE ≥18 and ≤26
  6. Absence of major depressive disease according to GDS of < 5
  7. Modified Hachinski Ischemic Scale ≤4
  8. Formal education for eight or more years
  9. Previous decline in cognition for more than six months as documented in patient medical records
  10. A caregiver available and living in the same household or interacting with the patient a sufficient time each week and available if necessary to assure administration of drug
  11. Patients living at home or nursing home setting without continuous nursing care
  12. General health status acceptable for a participation in a 6-month clinical trial
  13. Ability to swallow capsules
  14. Stable pharmacological treatment of any other chronic condition for at least one month prior to screening
  15. Stable treatment with one of the acetylcholinesterase inhibitors donepezil (Aricept ®), galantamine (Razadyne®), or rivastigmine (Exelon) or the partial NMDA receptor antagonist with memantine (Namenda®) at least 3-months before baseline Visit or Combination of both treatments mentioned above
  16. No regular intake of prohibited medications as noted in Section 11.8 of the protocol
  17. Signed informed consent by the patient, examined and verified to be mentally capable by an independent physician, prior to the initiation of any study specific procedure. Signed consent of the caregiver (see inclusion criteria 10).

Exclusion Criteria:

  1. Failure to perform screening or baseline examinations
  2. Hospitalization or change of chronic concomitant medication one month prior to screening or during screening period
  3. Clinical, laboratory or neuro-imaging findings consistent with:

    • Other primary degenerative dementia, (dementia with Lewy bodies, fronto-temporal dementia, Huntington's disease, Creutzfeldt-Jakob Disease, Down's syndrome, etc.)
    • Other neurodegenerative condition (Parkinson's disease, amyotrophic lateral sclerosis, etc.)
    • Cerebrovascular disease (major infarct, one strategic or multiple lacunar infarcts, extensive white matter lesions > one quarter of the total white matter)
    • Other central nervous system diseases (severe head trauma, tumors, subdural hematoma or other space occupying processes, etc.)
    • Seizure disorder
    • Other infectious, metabolic or systemic diseases affecting central nervous system (syphilis, present hypothyroidism, present vitamin B12 or folate deficiency, serum electrolytes out of normal range, juvenile onset diabetes mellitus, etc.)
  4. A current DSM-IV diagnosis of active major depression, schizophrenia or bipolar disorder
  5. Clinically significant, advanced or unstable disease that may interfere with primary or secondary variable evaluations, and which may bias the assessment of the clinical or mental status of the patient or put the patient at special risk, such as:

    • chronic liver disease, liver function test abnormalities or other signs of hepatic insufficiency (ALT, AST, Gamma GT, alkaline phosphatase > 2.5 ULN)
    • Respiratory insufficiency
    • Renal insufficiency (serum creatinine >2mg/dl) or creatinine clearance ≤ 30 mL/min according to Cockcroft-Gault formula). In case of creatinine clearance ≤30mL/min, an alternative verification of the renal function must be completed using Cystatin C analysis. In case of normal level of Cystatin C, the patient can be included
    • Heart disease (myocardial infarction, unstable angina, heart failure, Cardiomyopathy within six months before screening)
    • Bradycardia (heart beat <50/min.) or tachycardia (heart beat >95/min.)
    • Hypertension (>180/95) or hypotension requiring treatment with more than three drugs
    • AV block (type II / Mobitz II and type III), congenital long QT syndrome, sinus node dysfunction or prolonged QTcB-interval (males >450 and females >470 msec)
    • Uncontrolled diabetes defined by HbA1c >8.5
    • Malignant tumors within the last five years except skin malignancies (other than melanoma) or indolent prostate cancer
    • Metastases
  6. Disability that may prevent the patient from completing all study requirements (e.g. blindness, deafness, severe language difficulty, etc.)
  7. Women who are fertile and of childbearing potential
  8. Chronic daily drug intake of ≥ 14 days or expected for ≥ 14 days:

    • benzodiazepines, neuroleptics or major sedatives
    • Antiepileptics
    • Centrally active anti-hypertensive drugs (clonidine, l-methyl DOPA, guanidine, guanfacine, etc.)
    • Opioid containing analgesics
  9. Nootropic drugs with exception of Ginko Biloba
  10. Suspected or known drug or alcohol abuse, i.e. more than approximately 60 g alcohol (approximately 1 liter of beer or 0.5 liter of wine) per day indicated by elevated MCV significantly above normal value at screening
  11. Suspected or known allergy to any components of the study treatments
  12. Enrollment in another investigational study or intake of investigational drug within the previous three months
  13. Any condition, which, in the opinion of the investigator, makes the patient unsuitable for inclusion
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03069014


Contacts
Contact: Nikola Helmberg, PhD 0043 3132 40444 ext 12 nhelmberg@neuroscios.com
Contact: Nina Funk, MSc 0043 3132 40444 ext 14 nfunk@neuroscios.com

Locations
Austria
University Hospital Graz Recruiting
Graz, Styria, Austria, 8034
Contact: Birgit Reinhart    +43 316 385 833 96    birgit.reinhart@medunigraz.at   
Principal Investigator: Reinhold Schmidt, Prof. Dr.         
Sub-Investigator: Anita Lechner, Dr. med.         
Landeskrankenhaus Hall Recruiting
Hall in Tirol, Tirol, Austria, 6060
Contact: Elisabeth Klingler    +43 50504 88265    elisabeth.klingler@tirol-kliniken.at   
Principal Investigator: Douglas Imarhiagbe, OA Dr. med.         
Sub-Investigator: Cornelia Hessler-Piock, Dr. med.         
Czech Republic
Charles University Not yet recruiting
Praha, Hlavni mesto PRAHA, Czech Republic, 16000
Contact: Marcela Sedlackova    +42 5 0083 6974    marcelasedlackova@seznam.cz   
Principal Investigator: Jakub Hort, Prof. MD         
Sub-Investigator: Jan Lazco, MD         
Neurology Clinic of Martin Urbanek Not yet recruiting
Brno, Jihomoravsky kraj, Czech Republic, 60200
Contact: Jana Pacinkova    00420 737 157 670    j.pacinkova@gmail.com   
Principal Investigator: Katerina Sheardová, MD         
Sub-Investigator: Martin Urbanek, MD         
Vestra clinics s.r.o Recruiting
Rychnov nad Kneznou, Kralovehadrecky kraj, Czech Republic, 51601
Contact: Jitka Adamcova    +42 0607 818683    jitka@vestraclinics.org   
Principal Investigator: Ladislav Pazdera, MD         
Sub-Investigator: Josef Laza, MD         
NEUROHK s.r.o Not yet recruiting
Chocen, Pardubicky kraj, Czech Republic, 56501
Contact: Jiri Kucera    +420 604 187 410    kucerjiri@gmail.com   
Principal Investigator: Martin Valis, MD         
Sub-Investigator: Petr Barton, MD         
Germany
Klinikum Nürnberg Nord Not yet recruiting
Nurnberg, Bayern, Germany, 90419
Contact: Claudia Reichold    +49 911 398-2829    Reichold@klinikum-nuernberg.de   
Principal Investigator: Günter Niklewski, Prof. Dr.Dr.         
Sub-Investigator: Katharina Hösl, OÄ Dr. med.         
Studienzentrum Nordwest Not yet recruiting
Westerstede, Niedersachsen, Germany, 26655
Contact: Irene Reinisch    +49 448852 1500    ireinisch@studienzentrum-nordwest.de   
Principal Investigator: Joachim Springub, Dr. med.         
Sub-Investigator: Wolfgang Schwarz, Dr. med.         
Sächsisches Krankenhaus Arnsdorf Not yet recruiting
Arnsdorf, Sachsen, Germany, 01477
Contact: Ramona Rost    +49 35200 26-2270    Ramona.Rost@skhar.sms.sachsen.de   
Principal Investigator: Peter Schönknecht, Prof. Dr.         
Sub-Investigator: Majdy Abu Bakr, OA Dr.         
Pharmakologisches Studienzentrum Chemnitz GmbH Not yet recruiting
Chemnitz, Sachsen, Germany
Contact: Anne Merkel    +49 3727 991006    merkel@mvz-mittweida.de   
Principal Investigator: Ralf Bodenschatz, Dipl.-med.         
Sub-Investigator: Gunter Schumann, Dr. med.         
Charité Universitätsmedizin Berlin Not yet recruiting
Berlin, Germany, 12203
Contact: Brigitte Haas, Dr.rer.nat.    +49 3045 0517657    brigitte.haas@charite.de   
Principal Investigator: Oliver Peters, Doz. Dr.         
Sub-Investigator: Britta Jänen, Dr. med.         
Sweden
Karolinska University Not yet recruiting
Stockholm, Stockholms Iän, Sweden, 14186
Contact: Malin Aspö    +46 8 585 854 68    malin.aspo@karolinska.se   
Principal Investigator: Niels Andreasen, Prof.Dr.         
Sponsors and Collaborators
PharmatrophiX Inc.
National Institute on Aging (NIA)
Investigators
Principal Investigator: Manfred Windisch, PhD NeuroScios GmbH
  More Information

Responsible Party: PharmatrophiX Inc.
ClinicalTrials.gov Identifier: NCT03069014     History of Changes
Other Study ID Numbers: NSC15001
2015-005263-16 ( EudraCT Number )
1R01AG051596-01A1 ( U.S. NIH Grant/Contract )
First Submitted: February 3, 2017
First Posted: March 3, 2017
Last Update Posted: March 3, 2017
Last Verified: February 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders